ArticleMolecular psychiatry2021
APOE2 mitigates disease-related phenotypes in an isogenic hiPSC-based model of Alzheimer's disease.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Advances in hiPSC-Derived Brain Organoids as a Model to Study Neuroinflammation in Alzheimer's Disease.Journal of neurochemistry · 2026Review
- APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer's Disease and Cardiovascular Disease.Molecular neurobiology · 2025Review
- APOE4 to APOE2 allelic switching in mice improves Alzheimer's disease-related metabolic signatures, neuropathology and cognition.Nature neuroscience · 2025Article
- Development of an electroconductive Heart-on-a-chip model to investigate cellular and molecular response of human cardiac tissue to gold nanomaterials.Biomaterials · 2025Article
- Molecular mechanisms and biomarkers in neurodegenerative disorders: a comprehensive review.Molecular biology reports · 2025Review
- Synthesis and Characterization of Transferrin and Cell-Penetrating Peptide-Functionalized Liposomal Nanoparticles to Deliver Plasmid ApoE2Molecular pharmaceutics · 2025Article
- Altered metabolic function induced by Aβ-oligomers and PSEN1 mutations in iPSC-derived astrocytes.Journal of neurochemistry · 2025Article
- From Lab Bench to Hope: Emerging Gene Therapies in Clinical Trials for Alzheimer's Disease.Molecular neurobiology · 2025Review
- Engineered Gold and Silica Nanoparticle-Incorporated Hydrogel Scaffolds for Human Stem Cell-Derived Cardiac Tissue Engineering.ACS biomaterials science & engineering · 2024Article
- PINE-TREE enables highly efficient genetic modification of human cell lines.Molecular therapy. Nucleic acids · 2023Article
- APOE deficiency impacts neural differentiation and cholesterol biosynthesis in human iPSC-derived cerebral organoids.Stem cell research & therapy · 2023Article
- Immortalized hippocampal astrocytes from 3xTg-AD mice, a new model to study disease-related astrocytic dysfunction: a comparative review.Neural regeneration research · 2023Review
- Advances in Molecular Psychiatry - March 2023: mitochondrial function, stress, neuroinflammation - bipolar disorder, psychosis, and Alzheimer's disease.Molecular psychiatry · 2023Article
- Endotype reversal as a novel strategy for screening drugs targeting familial Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- A microcarrier-based protocol for scalable generation and purification of human induced pluripotent stem cell-derived neurons and astrocytes.STAR protocols · 2022Article
- Calcium Ions Aggravate Alzheimer's Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits.Frontiers in molecular neuroscience · 2021Review
- The Emergence of Model Systems to Investigate the Link Between Traumatic Brain Injury and Alzheimer's Disease.Frontiers in aging neuroscience · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Genome-wide association studies (GWAS) have identified polymorphism in the Apolipoprotein E gene (APOE) to be the most prominent risk factor for Alzheimer's disease (AD). Compared to individuals homozygous for the APOE3 variant, individuals with the APOE4 variant have a significantly elevated risk of AD. On the other hand, longitudinal studies have shown that the presence of the APOE2 variant reduces the lifetime risk of developing AD by 40 percent. While there has been significant research that has identified the risk-inducing effects of APOE4, the underlying mechanisms by which APOE2 influences AD onset and progression have not been extensively explored. In this study, we utilize an isogenic human induced pluripotent stem cell (hiPSC)-based system to demonstrate that conversion of APOE3 to APOE2 greatly reduced the production of amyloid-beta (Aβ) peptides in hiPSC-derived neural cultures. Mechanistically, analysis of pure populations of neurons and astrocytes derived from these neural cultures revealed that mitigating effects of APOE2 are mediated by cell autonomous and non-autonomous effects. In particular, we demonstrated the reduction in Aβ is potentially driven by a mechanism related to non-amyloidogenic processing of amyloid precursor protein (APP), suggesting a gain of the protective function of the APOE2 variant. Together, this study provides insights into the risk-modifying effects associated with the APOE2 allele and establishes a platform to probe the mechanisms by which APOE2 enhances neuroprotection against AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.